Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: ICA1

Gene summary for ICA1

Gene summary.

Gene information	Species	Human
	Gene symbol	ICA1
	Gene ID	3382
	Gene name	islet cell autoantigen 1
	Gene Alias	ICA69
	Cytomap	7p21.3
	Gene Type	protein-coding
	GO ID	GO:0002790
	UniProtAcc	A0A024RA29

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
3382	ICA1	HTA11_1938_2000001011	Human	Colorectum	AD	4.74e-02	3.85e-01	-0.0811
3382	ICA1	HTA11_99999965104_69814	Human	Colorectum	MSS	3.31e-11	8.39e-01	0.281
3382	ICA1	HTA11_99999974143_84620	Human	Colorectum	MSS	3.47e-04	-3.22e-01	0.3005
3382	ICA1	A001-C-207	Human	Colorectum	FAP	7.57e-05	1.84e-01	0.1278
3382	ICA1	A015-C-203	Human	Colorectum	FAP	1.77e-20	-1.79e-01	-0.1294
3382	ICA1	A015-C-204	Human	Colorectum	FAP	3.46e-04	-6.83e-02	-0.0228
3382	ICA1	A014-C-040	Human	Colorectum	FAP	1.63e-04	1.85e-01	-0.1184
3382	ICA1	A002-C-201	Human	Colorectum	FAP	4.69e-13	-2.96e-01	0.0324
3382	ICA1	A002-C-203	Human	Colorectum	FAP	1.67e-05	3.29e-01	0.2786
3382	ICA1	A001-C-119	Human	Colorectum	FAP	1.51e-06	8.93e-02	-0.1557
3382	ICA1	A001-C-108	Human	Colorectum	FAP	2.80e-10	2.19e-01	-0.0272
3382	ICA1	A002-C-205	Human	Colorectum	FAP	3.48e-23	-1.94e-01	-0.1236
3382	ICA1	A001-C-104	Human	Colorectum	FAP	7.99e-04	3.03e-01	0.0184
3382	ICA1	A015-C-005	Human	Colorectum	FAP	5.29e-03	3.87e-02	-0.0336
3382	ICA1	A015-C-006	Human	Colorectum	FAP	4.87e-15	-1.16e-02	-0.0994
3382	ICA1	A015-C-106	Human	Colorectum	FAP	4.24e-06	3.93e-02	-0.0511
3382	ICA1	A002-C-114	Human	Colorectum	FAP	1.14e-16	-1.47e-01	-0.1561
3382	ICA1	A015-C-104	Human	Colorectum	FAP	2.14e-22	-5.20e-02	-0.1899
3382	ICA1	A001-C-014	Human	Colorectum	FAP	7.05e-11	2.45e-01	0.0135
3382	ICA1	A002-C-016	Human	Colorectum	FAP	2.63e-17	-1.37e-01	0.0521

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Lung		AAH: Atypical adenomatous hyperplasia
		AIS: Adenocarcinoma in situ
		IAC: Invasive lung adenocarcinoma
		MIA: Minimally invasive adenocarcinoma
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Prostate		BPH: Benign Prostatic Hyperplasia
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:0050708	Colorectum	AD	regulation of protein secretion	83/3918	268/18723	6.59e-05	1.07e-03	83
GO:0009306	Colorectum	AD	protein secretion	105/3918	359/18723	1.05e-04	1.57e-03	105
GO:0035592	Colorectum	AD	establishment of protein localization to extracellular region	105/3918	360/18723	1.18e-04	1.73e-03	105
GO:0071692	Colorectum	AD	protein localization to extracellular region	106/3918	368/18723	1.86e-04	2.49e-03	106
GO:0050796	Colorectum	AD	regulation of insulin secretion	54/3918	165/18723	2.60e-04	3.25e-03	54
GO:0030073	Colorectum	AD	insulin secretion	61/3918	195/18723	4.28e-04	4.81e-03	61
GO:0015833	Colorectum	AD	peptide transport	77/3918	264/18723	8.90e-04	8.60e-03	77
GO:0090087	Colorectum	AD	regulation of peptide transport	60/3918	202/18723	1.94e-03	1.58e-02	60
GO:0030072	Colorectum	AD	peptide hormone secretion	68/3918	236/18723	2.39e-03	1.85e-02	68
GO:0002791	Colorectum	AD	regulation of peptide secretion	59/3918	200/18723	2.50e-03	1.92e-02	59
GO:0090276	Colorectum	AD	regulation of peptide hormone secretion	58/3918	196/18723	2.51e-03	1.92e-02	58
GO:0002790	Colorectum	AD	peptide secretion	69/3918	242/18723	2.97e-03	2.22e-02	69
GO:0042886	Colorectum	AD	amide transport	83/3918	301/18723	3.37e-03	2.46e-02	83
GO:00507082	Colorectum	MSS	regulation of protein secretion	78/3467	268/18723	1.47e-05	3.33e-04	78
GO:00093062	Colorectum	MSS	protein secretion	98/3467	359/18723	2.43e-05	5.09e-04	98
GO:00355922	Colorectum	MSS	establishment of protein localization to extracellular region	98/3467	360/18723	2.75e-05	5.58e-04	98
GO:00716922	Colorectum	MSS	protein localization to extracellular region	99/3467	368/18723	4.17e-05	7.83e-04	99
GO:00507962	Colorectum	MSS	regulation of insulin secretion	50/3467	165/18723	1.61e-04	2.31e-03	50
GO:00300732	Colorectum	MSS	insulin secretion	56/3467	195/18723	3.21e-04	4.18e-03	56
GO:00158332	Colorectum	MSS	peptide transport	71/3467	264/18723	4.79e-04	5.60e-03	71

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Enriched KEGG pathways.

Pathway ID

Tissue

Disease Stage

Description

Gene Ratio

Bg Ratio

pvalue

p.adjust

qvalue

Count

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

ICA1

SNV

Missense_Mutation

c.473N>A

p.Arg158His

p.R158H

Q05084

protein_coding

deleterious(0.04)

benign(0.424)

TCGA-AP-A1DV-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

ICA1

SNV

Missense_Mutation

rs138213995

c.1387G>A

p.Asp463Asn

p.D463N

Q05084

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-AX-A06D-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

III/IV

Chemotherapy

carboplatin

ICA1

SNV

Missense_Mutation

rs776544773

c.484T>C

p.Cys162Arg

p.C162R

Q05084

protein_coding

deleterious(0.01)

benign(0.202)

TCGA-AX-A0J0-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

ICA1

SNV

Missense_Mutation

rs768714490

c.98N>T

p.Thr33Met

p.T33M

Q05084

protein_coding

deleterious(0)

probably_damaging(0.998)

TCGA-AX-A0J1-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

ICA1

SNV

Missense_Mutation

c.1196G>C

p.Gly399Ala

p.G399A

Q05084

protein_coding

deleterious(0.03)

probably_damaging(1)

TCGA-B5-A1MY-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

III/IV

Chemotherapy

carboplatin

ICA1

SNV

Missense_Mutation

rs760153189

c.595N>T

p.Arg199Cys

p.R199C

Q05084

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-B5-A3FA-01

Endometrium

uterine corpus endometrioid carcinoma

Female

>=65

I/II

Unknown

ICA1

SNV

Missense_Mutation

novel

c.998C>T

p.Ser333Phe

p.S333F

Q05084

protein_coding

tolerated(0.29)

benign(0)

TCGA-B5-A3FC-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

ICA1

SNV

Missense_Mutation

novel

c.1192N>C

p.Phe398Leu

p.F398L

Q05084

protein_coding

deleterious(0.02)

probably_damaging(0.983)

TCGA-D1-A175-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Chemotherapy

paclitaxel

ICA1

SNV

Missense_Mutation

rs150710019

c.407G>A

p.Arg136Gln

p.R136Q

Q05084

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-D1-A17Q-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

ICA1

SNV

Missense_Mutation

rs745319774

c.277G>A

p.Glu93Lys

p.E93K

Q05084

protein_coding

deleterious(0.01)

probably_damaging(0.976)

TCGA-D1-A17Q-01

Endometrium

uterine corpus endometrioid carcinoma

Female

<65

I/II

Unknown

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID	Symbol	Category	Interaction Types	Drug Claim Name	Drug Name	PMIDs
3382	ICA1	NA		tramadol	TRAMADOL	30971809
3382	ICA1	NA		o-desmethyl-tramadol		30971809
3382	ICA1	NA		o-desmethyltramadol		30971809

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